treatments are possible and even likely. Last December, he
published a paper showing corrections of several rare mutations—again in cells in a lab dish, including some taken from
a child with dwarfism and others from another boy with
Duchenne. That boy, named Gavriel Rosenfeld, is the son of
close friends of Cohn’s in London. They run a charitable foundation that Cohn advises.

Cohn is a newcomer to CRISPR. A few years ago, he was
studying hibernating squirrels. They don’t move for months,
yet their muscles aren’t any worse for it. That is the sort of “we
might just find something” approach favored in basic-research
labs. Now, with gene editing, he sees a direct path to cur-ing someone he knows. Gavriel is 14, and since correcting his
cells, Cohn’s lab has also created a mouse model that shares
his mutation. Like Dupree’s, the mutation is one of a kind, and
within a few weeks Cohn’s lab will start treating the mice.

But then what? Cohn says he doesn’t know. How would youeven test a drug designed for one person? Who would pay forit? He says he visited Health Canada, the country’s regulator,and was told to come back if he cured the mice. “This is goingto require a significant rethinking,” he says. “And the fact thatyou and I are having this conversation is the beginning of theparadigm shift.”Cohn’s approach of correcting individual mutations hasstirred hopes among parents of boys with Duchenne. “This isa CURE!!!” one wrote on the Web. His lab has used CRISPRto fix mutations in cells taken from several boys he knows, anda waiting list he keeps in a spreadsheet currently lists 53 chil-dren with muscular dystrophy. The parents of all of them wantto know if their child could be helped by gene editing.

If a gene-therapy study like the one Olson plans is successful, and if CRISPR reaches enough muscle cells, there
might be a strong argument that a one-off treatment would
work. After all, to aim at a new mutation all you’d do is tweak
the component of CRISPR that zeroes in on a specific DNA
sequence. The price of manufacturing a single dose also might
not be an obstacle. Two existing gene therapies approved in
Europe cost $1 million and $665,000. Even if it cost twice
that, a one-time gene fix with CRISPR would be cheaper than
a lifetime of costly drugs, wheelchairs, and dependency.

In holding out the hope of individual cures, Cohn admitshe’s created some new problems. He has invited parents tothe lab, and little boys have tottered among the lab stools. Butduring a three-hour lab meeting this fall, he and his studentsdecided to stop referring to “Gavriel’s cells” or “Jake’s cells”and use numerical code names instead. They still know who iswho, but this gives them space to be impartial. “I know in theback of my head, but you want to stay unbiased,” a graduatestudent in the lab, Tatianna Wong, told me. “I can’t work onthis case just because I feel bad for him. I have scientific ques-tions to answer.”

High expectations

Some veterans of gene therapy roll their eyes when they hear
what newcomers think CRISPR will do. I visited the vector
development center at St. Jude, touring a cramped L-shaped
lab with Byoung Ryu, an expert in making viruses, who
chopped the air above his head and said, “People’s expectations
are up here.” Ryu warns that basic, unresolved biological problems remain. One is whether editing will work often enough
in cells such as those in the bone marrow, the type that need
to be changed to correct sickle-cell disease. If too few cells end
up edited, the treatments won’t be effective. “It’s a numbers
game,” says Ryu.

Ryu was the first employee at a Boston-area gene-therapycompany, Bluebird Bio, whose stock price staggered down thechart after its first few patients didn’t all respond the sameway. “I’m not negative on CRISPR, but there is a reality check,”Ryu says. “It’s not coming to people next year. It works in thepetri dish every single time, but my perspective is that genomeediting may happen in the future but not in the near term.”Side effects could also be an obstacle. CRISPR has thepotential to cause accidental, unwanted edits that could not beerased if they ended up written into a person’s genome. Cur-rently, researchers rely on academic computer programs topredict such effects. (One, maintained at Harvard, is calledCHOPCHOP.) But a program can’t predict everything. Twoearly tests of gene therapy, in the 2000s, accidentally causedleukemia in several children. No one had anticipated that con-sequence of changing the genome. Although Olson says hehas not seen ill effects in his mice, he allows that CRISPR cancause “inadvertent changes in DNA that are important for life.”And editing billions of individual cells in a person’s body, sci-entists acknowledge, will be the surest way to discover howCRISPR can go wrong.